Transdermal drug delivery is a highly regarded and utilized route due to known efficacy and patient compliance. However, Formulation difficulties arise when delivery systems are formulated to optimize drug loading. With variations in drug loading come formulation concerns relating to optimization of drug delivery across and through the various epidermal layers.
Various transdermal drug delivery systems are known, including liquids, creams, lotions, salves, pastes, balms, gels, and ointments. A matrix-type patch is a typical patch embodiment, and includes a pressure-sensitive adhesive coated onto an impermeable or non-occlusive backing. The adhesive layer, which is applied to the skin, includes the active ingredient, and releases the active ingredient via passive diffusion when it is adhered to the skin.
Other inactive ingredients such as menthol have been incorporated into patches to enhance the feel and smell of the product when applied to the skin. However, menthol will often react with other ingredients used in the paten formulation, or evaporate leading to an unstable product. Compounds known as sensates have been used in cosmetics to impart a cooling or heating sensation. Examples include methanediol, methoxypropanediol, isopulegol, and vanillyl butyl ether. Unlike menthol, these compounds are not highly volatile, and thus do not suffer the same stability problems as menthol.
Topical, local, and transdermal delivery systems can also be formulated to achieve particular blood level profiles of the drug, such as steady-state blood level profiles or increasing blood level profiles, as may be desired for a particular drug or condition. The release rate of the drug can be controlled by altering the polymers used for the adhesive or by the addition of permeation enhancers, solubility enhancers, co-solvents, dispersion agents, and/or crystallization inhibitors.
U.S. Pat. No. 4,72,5,272 describes a reservoir-type for nitroglycerin where a liquid reservoir of nitroglycerine is layered adjacent to a polyisobutylene adhesive layer, between the adhesive and the impermeable backing. The nitroglycerin migrates through the polyisobutylene when the patch is applied to the skin to deliver the active ingredient.
U.S. Pat. No. 8,187,628 describes the use of acrylic-based polymers as the matrix adhesive wherein the adhesive properties, the solubility of the drug in the adhesive matrix, and the rate of migration of active ingredient through the matrix are adjusted by optimizing the acrylic mixture.
U.S. Pat. No. 4,994,267 describes a multi-polymer system in which ethylene vinyl acetate polymers, acrylic polymers, natural or synthetic rubbers and a tackifying agent are used in combination with a medicament to achieve the desired wear and drug solubility.
U.S. Pat. No. 4,942,037 describes another reservoir-type patch in which the adhesive layer is made from a synthetic rubber, namely a silicone pressure sensitive adhesive.
In spite of these advances, there remains a need for transdermal patch formulations and packaging systems that that can be easily manufactured and have excellent stability when stored for prolonged periods of time.
One object of the present invention is to provide matrix-type patches for the delivery of lidocaine to the skin.
Another object is to provide formulations that allow for the release of lidocaine at therapeutically effective levels.
Yet another object is to provide formulations that are easily manufactured, and that remain stable for prolonged periods of time.
Another object is to provide ingredients that do not suffer from the same problems as menthol, and still enhance the feel or smell of the product when incorporated in the matrix adhesive.
Still another object is to provide packaging materials that support the stability of the formulation.